The general procedure for the synthesis of 2-bromo-5-methylbenzoic acid from 2-amino-5-methylbenzoic acid was as follows: CuSO4-5H2O (2.82 g, 11.3 mmol), NaBr (2.31 g, 22.4 mmol), and copper scrapings (1.50 g, 23.6 mmol) were boiled in 15 mL of 47% hydrobromic acid until the solution became colorless. Under heating conditions, 5-methyl-phthalamic acid (5.00 g, 33.1 mmol) was dissolved in a solvent mixture of 11.3 mL of 47% aqueous hydrobromic acid and 28 mL of water. The solution was slowly added to the above CuBr solution at 100°C. The temperature of the reaction mixture was maintained at 90-95°C and 25 mL of aqueous solution of NaNO2 (4.53 g, 65.7 mmol) was slowly added with stirring. Upon completion of the reaction, the precipitated acid was collected by diafiltration, washed with 10% aqueous hydrobromic acid and reprecipitated by adding concentrated hydrochloric acid to the alkaline solution. The crude product was treated by activated charcoal and recrystallized from water three times to give 4.00 g (18.6 mmol, 56% yield) of white crystals with melting point of 137-139°C (literature value: 137.6-139°C). The product was analyzed by IR, 1H NMR, 13C NMR and mass spectrometry to confirm the structure, and the results of elemental analyses were consistent with the theoretical values.
